Mechanism of Action: UDP Glucuronosyltransferases Inhibitors

Drugs with Mechanism of Action: UDP Glucuronosyltransferases Inhibitors

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Exclusivity Expiration
Amneal	ATAZANAVIR SULFATE	atazanavir sulfate	CAPSULE;ORAL	209717-001	Jun 1, 2020		DISCN	No	No
Aurobindo Pharma	ATAZANAVIR SULFATE	atazanavir sulfate	CAPSULE;ORAL	204806-003	Jun 25, 2018	AB	RX	No	No
Aurobindo Pharma	ATAZANAVIR SULFATE	atazanavir sulfate	CAPSULE;ORAL	204806-004	Jun 25, 2018	AB	RX	No	No
Hetero Labs Ltd Iii	ATAZANAVIR SULFATE	atazanavir sulfate	CAPSULE;ORAL	212278-001	Feb 2, 2022	AB	RX	No	No
Hetero Labs Ltd Iii	ATAZANAVIR SULFATE	atazanavir sulfate	CAPSULE;ORAL	212278-002	Feb 2, 2022	AB	RX	No	No
Hetero Labs Ltd Iii	ATAZANAVIR SULFATE	atazanavir sulfate	CAPSULE;ORAL	212278-003	Feb 2, 2022	AB	RX	No	No
Zydus Pharms	ATAZANAVIR SULFATE	atazanavir sulfate	CAPSULE;ORAL	210575-003	Jun 4, 2020		DISCN	No	No

UDP Glucuronosyltransferases Inhibitors Market Analysis and Financial Projection

The market dynamics and patent landscape for UDP-glucuronosyltransferase (UGT) inhibitors reflect their growing therapeutic and pharmacological relevance. Here's an analysis based on current developments and intellectual property trends:

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Market Dynamics

Therapeutic Applications

1. Parasitic Infections
   UGT inhibitors like FDA-approved compounds (e.g., atazanavir) show macrofilaricidal activity against Brugia malayi, a nematode causing lymphatic filariasis[1]. This positions UGT inhibitors as potential tools for neglected tropical disease eradication.

2. Oncology

   • Drug Resistance: Elevated UGT1A levels in acute myeloid leukemia (AML) are linked to glucuronidation-driven drug resistance. Inhibitors targeting UGT1A4 restore chemosensitivity in preclinical models[8][16].
   • Clinical Trials: Phase II trials (e.g., NCT02073838) combine UGT modulators like vismodegib with chemotherapy, showing reduced UGT1A levels in responders[16].

3. Metabolic and Cardiovascular Diseases

   • SGLT2 inhibitors (e.g., canagliflozin, dapagliflozin) rely partially on UGT-mediated metabolism. UGT inhibitors may mitigate drug-drug interactions (DDIs) or enhance bioavailability[4][13].
   • The global SGLT2 market, valued at $15.85B in 2023, indirectly drives demand for UGT interaction studies[13].

Regulatory Drivers

• FDA and EMA require UGT inhibition assessments in drug development to avoid adverse DDIs[3][9].
• Up to 10% of top prescribed drugs use glucuronidation as a clearance mechanism, necessitating standardized in vitro testing (e.g., Cyprotex’s IC50/Ki assays)[3][11].

Challenges

• Enzyme Complexity: Overlapping substrate specificities and polymorphisms (e.g., UGT1A1 in Gilbert’s syndrome) complicate inhibitor design[3][6][9].
• Clinical Relevance: UGT-mediated DDIs often result in <2-fold exposure changes, reducing perceived urgency despite risks in polypharmacy[15].

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Patent Landscape

Key Innovations

1. UGT Inhibitors as Bioenhancers

   • US20030215462A1: Co-administration of UGT inhibitors (e.g., quercetin, gallates) with drugs like raloxifene or morphine to boost bioavailability[2].
   • US20060040875A1: Natural compounds (e.g., capillarisin, isorhamnetin) as UGT2B inhibitors to enhance opioid efficacy[14].

2. Therapeutic Targeting

   • US8841350B2: Pterostilbene induces UGT activity for detoxification in proliferative disorders[10].
   • JP5133064B2: UGT2B inhibitors/enhancers (e.g., nordihydroguaiaretic acid) for metabolic modulation[17].

3. Structural and Allosteric Approaches
   Novel small molecules targeting UGT1A-C domains show isoform specificity (e.g., UGT1A4 vs. UGT2B7 inhibition), reducing off-target effects[8].

Competitive Trends

• Focus on Specific Isoforms: Patents prioritize UGT1A1, UGT1A9, and UGT2B7 due to roles in bilirubin/drug metabolism[3][6][12].
• Natural Compounds: Over 50% of patented inhibitors derive from plant metabolites (e.g., sauchinone, wogonin)[7][9][14].
• Combination Therapies: Synergy with albendazole (antiparasitic) or decitabine (chemotherapy) underscores strategic partnerships[1][16].

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Market Outlook

• Growth Drivers: Rising demand for DDI management, oncology resistance solutions, and parasite eradication programs.
• Regional Trends: North America leads in regulatory-compliant testing services, while Asia-Pacific explores cost-effective natural inhibitors[13].
• Innovation Frontiers:
  • Allosteric inhibitors targeting non-catalytic UGT domains[8].
  • Bioinformatics-driven drug design to resolve structural bottlenecks[6].

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Key Takeaway
The UGT inhibitor market is evolving from ancillary DDI tools to central players in precision medicine, driven by isoform-specific patents and unmet needs in oncology and infectious diseases. Regulatory mandates and structural biology advances will shape next-generation therapies.

References

1. https://journals.plos.org/plosntds/article?id=10.1371%2Fjournal.pntd.0007687
2. https://patents.google.com/patent/US20030215462A1/en
3. https://www.evotec.com/uploads/download-files/A-SciencePool_Downloads/Factsheet_Downloads/Cyprotex-UGT-Inhibition-Fact-Sheet.pdf
4. https://pmc.ncbi.nlm.nih.gov/articles/PMC7894401/
5. https://www.finnegan.com/en/insights/articles/the-immunotherapy-patent-landscape-types-of-patent-claims-for-immunotherapeutic-inventions.html
6. https://pubmed.ncbi.nlm.nih.gov/29484974/
7. https://www.mdpi.com/1420-3049/23/2/366
8. https://pubmed.ncbi.nlm.nih.gov/38043731/
9. https://pmc.ncbi.nlm.nih.gov/articles/PMC6437557/
10. https://patents.google.com/patent/US8841350B2/en
11. https://www.evotec.com/non-cyp-mediated-metabolism/ugt-inhibition
12. https://academic.oup.com/toxsci/article/61/1/49/1615282
13. https://www.grandviewresearch.com/industry-analysis/sglt2-inhibitors-market-report
14. https://patents.google.com/patent/US20060040875A1/en
15. https://pubmed.ncbi.nlm.nih.gov/37263383/
16. https://haematologica.org/article/view/haematol.2023.282791
17. https://patents.google.com/patent/JP5133064B2/en